Sickle cell anemia is a disorder in which the hemoglobin of the blood is primarily hemoglobin S. Hemoglobin S differs from normal hemoglobin in that valine is substituted for the normal glutamic acid in the 6-position of the .beta.-polypeptide chains of hemoglobin. As a result of this structural difference, the reduced hemoglobin S molecules then tend to stack into filaments which further aggregate into the elongated sickled cell.
Spontaneous sickling of such red cells occur when the concentration is sufficiently high but it is further facilitated by anoxia, acidosis, hyperthemia or excessive chilling. Thus, factors such as fever, an infection, or exposure to cold contribute to the formation of reduced hemoglobin S thus increasing the concentration of this material with a resultant increase in sickling. The sickling process is generally reversible although it does eventually reach a point at which it is irreversible. When the irreversible stage is passed, the cells involved are removed from the circulation resulting in a deficiency of such cells in the circulation and chronic hemolytic anemia. As a consequence, the ordinary symptoms associated with anemia would be observed. In addition, the cells formed deposit on the walls of the blood vessels and this would then impede circulation in the blood vessels and bring about painful vaso-occlusive crises. An increase in blood viscosity also occurs.
Previous treatments of sickle cell anemia have been purely symptomatic involving the administration of sedatives to alleviate the pain or, when a prolonged severe painful crisis is involved, by the administration of multiple packed cell transfusion which serves to reduce the proportion of circulating sickling prone red cells below a level that can be induced to sickle.
As the mechanism of the sickling disorder has become known, various drugs have been investigated in an attempt to find a satisfactory one that would be effective against sickling. Sodium cyanate has produced improvements but it has been considered difficult and dangerous to use because it produces neuropathies. Urea was discarded after a double-blind study. It was found to be no more or less effective than hydration alone. Steroid hromones can be used but only in adults. Other materials that have been investigated are dimethyl adipimate, ergot alkaloids and vincamines but the effectiveness of these materials is still unclear.